Obesity is a pathologic disorder caused by excess fat accumulation in various tissues. Excess food-intake of high fat content, lack of exercise, and genetic, environmental and psychological factors are the causes of obesity. Obsesity is considered as a direct or indirect cause of diabetes mellitus, cardiovascular diseases and short life expectation. A multitue of approaches and researches have been made to prevent and treat obesity but have finally failed to effectively treat obesity. Although many patients make various efforts such as diet-control, rigorous exercise and chemotherapy to prevent and treat obesity, they tend to return to obese state when they stop those efforts.

SynLeptin of Yonsei University has been developed on the basis of findings that the Tat polypeptide derived from HIV (Human Immunodeficiency Virus) and various peptides derived from Tat have excellent anti-obesity activity. Among Tat-derived peptides, two peptides originated from Tat that are called SynLeptin-1 and SynLeptin-2, respectively, are very effective in reducing the fat mass in vivo. SynLeptin-1 comprisese 71 amino acid residues of Tat and SynLeptin-2, 86 amino acid residues of Tat. The rabbits subcutanesouly administered with the two peptides were observed to be decreaseed in body weight. Among two peptides, SynLeptin-2 has been analzyed to exhibit more prominent inhibition action to fat mass than SynLeptin-1. The representative analysis results of SynLeptin-2 for anti-obesity activities are as follows: The SynLeptin-2 peptide was prepared in the fusion form with GST (glutathione-S-transferase).

The subcutaneous injection of GST-SynLeptin-2 exhibited an average of 10.73 g reduction in body weight compared with control mice as determined on day 100 post-treatment.

The SynLeptin-2 peptide decreases food intake by appetite inhibitory action, which can be reversed by appetite stimulant AGRP.

The pharmacokinetics of SynLeptin-2 has been studied by our laboratory (see Shin BS, et al. (2007) Pharmacokinetics of GST-TatdMt, a recombinant fusion protein possessing potent anti-obesity activity, in mice. Arch Pharm Res. 30(9):1162-7). The absolute bioavailability of SynLeptin-2 was 42.8% and 60.5% after p.o. and i.p. administration, respectively. Given the cell-penetrating potential, SynLeptin-2 may be absorbed into the systemic circulation to a relatively high extent after extravascular administration such as subcutaneous administration.